Caspofungin is a macrocyclic lipopeptide echinocandin whose structural formula is disclosed in column 2, lines 32-52 of U.S. Pat. No. 5,952,300. Caspofungin is also described in U.S. Pat. No. 5,378,804, and methods for its preparation are described in U.S. Pat. No. 5,378,804, U.S. Pat. No. 5,552,521, U.S. Pat. No. 5,952,300 and U.S. Pat. No. 6,136,783. Caspofungin is an inhibitor of the synthesis of β-(1,3)-D-glucan, which is an integral part of the fungal cell wall. Caspofungin is useful as an antibiotic, especially as an antifungal agent or as an antiprotozoal agent. As an antifungal agent, it is useful for the control of both filamentous fungi and yeast. It is especially adaptable to be employed for the treatment of mycotic infections in mammals, especially those caused by Candida species such as C. albicans, C. tropicalis, C. krusei, C. glabrata and C. pseudotropicalis, and Aspergillus species such as A. fumigatus, A. flavus and A. niger. In particular, the compound has been found effective against putatively Amphotericin B- and Fluconazole-resistant Candida isolates. The compound is also useful for the treatment and/or prevention of Pneumocystis carinii pneumonia to which immune compromised patients, such as those suffering from AIDS, are especially susceptible.
Caspofungin is typically employed in a lyophilized composition that is reconstituted for intravenous infusion. Preferred lyophilized caspofungin compositions are acetate-buffered products such as those described in U.S. Pat. No. 5,952,300. Of particular interest is the lyophilized, acetate-buffered product containing caspofungin in the form of a diacetate salt, sucrose, mannitol, glacial acetic acid, and sodium hydroxide. Such a product is available from Merck & Co., Inc. under the trade name CANCIDAS in 35 mg, 50 mg, and 70 mg doses. CANCIDAS is indicated for empirical therapy for fungal infection in patients with fever and neutropenia, the treatment of Candidemia and certain other Candida infections, the treatment of esophageal Candidiasis, and the treatment of invasive Aspergillosis in patients who are resistant to or cannot tolerate other therapies.
Lyophilized, acetate-buffered, caspofungin products such as CANCIDAS are characterized by good storage stability at low temperature (e.g., 2° C. to 8° C.) under ambient storage conditions. More particularly, the compositions can be stored at low temperature (e.g., 5° C.) for many months with minimal formation of degradates. Nonetheless, lyophilized caspofungin-containing products with improved storage stability at low temperatures and/or satisfactory storage stability at higher temperatures is desirable. Improved storage stability at about 5° C. would provide for a longer shelf life thereby reducing the potential for product loss. Satisfactory storage stability at room temperature would eliminate the need for refrigeration and the special handling and extra costs associated therewith.